Zinc pyrithione (ZPTO), also known as zinc pyridine-2-thiol-N-oxide or bis-[1-hydroxy-2(H) pyridinethionato]-zinc is a broad spectrum antimicrobial agent and has been used as fungicide and bactericide in various personal care and pharmaceutical products, particularly in anti-dandruff shampoos. ZPTO is also used as a biologically active agent for cutting oils and coolant systems, as an agent for protecting cellulosic fibres from loss of tensile strength due to action of fungi and as a preservative for water based paints, coatings, adhesives, wet-state preservatives, hard surface cleaners, fabric care compositions, wood products, plastic products, medical products, fibres or any other application where microorganism growth must be stopped or slowed.
The antifungal and antimicrobial activity of ZPTO depends on the bio-availability of ZPTO molecule on scalp. Because of poor solubility in water (6-12 ppm), the concentration of ZPTO molecules in aqueous media and thereafter on hair and scalp also remains low, leading to poor bio-availability. Also, when used in personal care formulations, it produces white suspension that precipitate in the packaging bottle. Therefore, to overcome these disadvantages of low water solubility, precipitations and poor bio-availability, ZPTO is generally used in excess (1-2% w/w) but higher concentration of ZPTO lacks ready consumer acceptability due to harshness.
There had been many approaches to increase the solubilisation and antimicrobial efficacy of zinc pyrithione.
U.S. Pat. No. 3,636,213 discloses solubilisation of heavy metal pyrithione salts in common organic solvents and/or water by combination with primary alkyl and aryl monoamines or, polyalkyleneimines, preferably dodecyl amine and diglycol amine for use in hair dressings. The compositions have pH's from about 8.5-9.0.
U.S. Pat. No. 3,785,985 and U.S. Pat. No. 3,940,482 describe the solubilization of heavy metal pyrithione salts in water and detergent containing compositions with aliphatic polyamine. However, ZPTO solubilized in alcohol/water system using polyethylenimine has pH of about 9.0 or above and reducing pH less than 8.0 leads to precipitation of ZPTO in the system.
U.S. Pat. No. 4,835,149 discloses the use of alkanol and/or alkyl amines in the solublizing a metal pyrithione salt in the preparation of a shampoo effective for the treatment of seborrhea and dandruff. The amines include ethanolamine, diethanolamine, monoisopropylamine and others together with a cosmetically effective amount of an aminopolycarboxylic acid to regulate the pH of the system between 6.5-7.5.
U.S. Pat. No. 6,908,912 discloses a stable, soluble, antimicrobial composition where insoluble metal salts of pyrithione in combination with a zinc source (zinc salts, -oxides, -hydroxides, -borates, -sulfates, -chlorides etc.) were solubilised in an organic amine (1,2-alkanolamines and 1,3-alkanolamines) alone or in combination with a second organic amine (monomeric and polymeric forms of 1,2-alkyldiamines and 1,3-alkyldiamines). These compositions deliver higher concentration of pyrithione and zinc ions to an application (in-can preservatives and metalworking fluids) and thus provide enhanced biocidal efficacy against microorganisms and bio-films.
It is known that below pH 4.5 zinc complex dissociates into free pyrithione and above pH 9.5, zinc complex hydrolyzes to yield ionized pyrithione and zincate species. Both free and ionized pyrithione are biologically active but being much more water soluble than the zinc complex they are most susceptible to degradation from exposure to light or oxygen. In the patent applications cited above, where different types of amines have been used to solubilize ZPTO, either require pH adjustment, pre-formulation of the actives or give precipitate on pH adjustment. Also these prior arts do not disclose any improved or enhanced antifungal or antimicrobial activity particularly the anti-dandruff efficacy for the resulting solubilized ZPTO as compared to ZPTO suspensions. Further, it is extremely difficult to simultaneously attain superior hair sensory attributes along with higher anti-dandruff efficacy from ZPTO containing compositions (US 2006/0182696).
WO 20010095717 discloses that cationic polymers can increase the efficacy of zinc pyrithione in an anti-dandruff shampoos by enhancing the deposition and retention of the water insoluble ZPTO particles on scalp. Similarly polyethylenimine or the reaction product of polyethylenimine and ethylene oxide or propylene oxide (U.S. Pat. No. 3,489,686); water-soluble cationic nitrogen-containing polymers or nitrogen-substituted cellulose ether derivatives (U.S. Pat. No. 3,580,853) and piperidinum chloride (U.S. Pat. No. 3,761,417) have also been disclosed to increase the efficacy of ZPTO. However, the effect on adsorption of a metal pyrithione salt such as zinc pyrithione was not found sufficient for required or enhanced anti-dandruff efficacy.
U.S. Pat. No. 4,557,928 describes the use of acrylamide copolymer quaternium 41 and Methocel to create more efficacious zinc pyrithione anti-dandruff shampoo but these shampoos were found unstable over a long period of time.
Cationic surfactants such as amino or quaternary ammonium hydrophilic moieties has been used as cationic surfactant or emulsifying agent in hair conditioners, shampoos, anti-static formulations, fabric softeners and other cosmetics and toiletries preparations (EP 0034385, EP 0941061, US 2008/0057015, U.S. Pat. No. 8,506,942, US 2012/0064136, U.S. Pat. No. 8,206,694 and US 2012/0100092). Some of them like cetyl pyridinium chloride, is also commonly used as antiseptic and/or antimicrobial component at low concentrations (0.025-0.1%) in many OTC health care products (creams, dentifrices, deodorizing and antiperspirant preparations mouth washes, toothpastes, lozenges, throat sprays, cough syrups, nasal sprays and pre-moistened wipes) deodorant.
US 2007/0020221 describes the use of cetylpyridinium chloride (CPC) as a skin lightening or pigmentation reducing cosmetic agent in cosmetic compositions to regulate the condition of mammalian keratinous tissue particularly for preventing, retarding, and/or treating uneven skin tone.
US 2006/0241190 describes the specific utility of cetylpyridinium chloride in cosmetic compositions as a keratolytic active with SLES for the treatment of psoriasis, eczema and like skin disorders.
As antimicrobial active in shampoos and/or hair care products, US 2011/0287074 describes the use of CPC as secondary antimicrobial agent in the form of a micro-emulsion. US 2012/012172 provides an antimicrobial composition with a synergistic effect of laurylamine oxide and CPC. This composition which has strong antimicrobial efficacy can be incorporated into shampoos for the treatment of fungal and/or bacterial infection on skin or mucosal surfaces.
Although the prior art describes that cationic polymers can enhance the deposition of ZPTO on scalp, it is extremely difficult to formulate their stable composition as they show problems in formulation compatibility particularly with ZPTO, resulting in loss of transparency, drop in viscosity and instability over a long period of time.
Thus, there is a need to develop antimicrobial stock compositions and/or personal care formulations with ZPTO in such a manner that ZPTO remains solubilised, maintains transparency above 90%, remains stable in wide pH range and storage conditions, aesthetically more desirable and simultaneously imparts high anti-dandruff efficacy at low concentration of active(s).